General Information on Food Intake
The human body normally functions in two states: food intake state and a fasting state. The duration and frequency of these states varies from individual to individual. Numerous factors are involved including availability of food as well as psychological and physiological condition.
Regarding food intake, nearly all of the body's energy comes from glucose and fatty acids. After being absorbed in the gastrointestinal tract (GIT), glucose can be taken up by cells and oxidized to generate ATP; linked with other glucose molecules and stored as glycogen; and combined with other glucose molecules and formed into fatty acids. Fatty acids, after being absorbed in the GIT can be oxidized to produce ATP or taken up by cells, combined with glycerol and stored as triglycerides. When a person has a positive energy balance, the hormone insulin plays a primary role in control of metabolic fuel metabolism. The pancreas secretes insulin in response to food intake. Insulin prepares the body for a sudden increase in metabolic fuels by facilitating glucose entry into cells for oxidation or storage. However, insulin inhibits release of fatty acids from fat cells. Absence of insulin (diabetes mellitus) leads to a buildup of blood glucose (hyperglycemia). Common diabetes disorders are type 1 where the body cannot produce insulin and type 2 where the body becomes less responsive to insulin.
Regarding fasting, the body normally relies on conversion of stored metabolic fuels. For example, the body breaks down glycogen and triglycerides to glucose and fatty acids. While the heart is a fatty acid burner, the brain relies on glucose. A group of hormones, sometimes referred to as counterregulatory hormones, mediate the breakdown and mobilization process. These hormones act, in general, counter to the actions of insulin and include epinephrine, glucagon and cortisol/corticosterone.
As discussed herein, various neural circuits control food intake and fasting hormones. Neural processes receive information, communicate information and respond to such information to thereby motivate the individual for food intake or not. While internal information affects such motivated behavior, at times, external information plays a role as well; thus, neural circuits that process internal and external information are involved.
As discussed in more detail below, mechanisms controlling food intake may include brain-based, peripheral-based and periphery to brain-based mechanisms. For example, inhibition of glucose oxidation in the caudal hindbrain increases food intake. Thus, the hindbrain, in contrast to the hypothalamus, contains cells that can monitor glucose availability and control food intake and epinephrine release. Peripheral mechanisms include those associated with the liver. Food passes through the liver where nutrients cause a decrease in food intake. In contrast, providing 2-deoxy-glucose (2DG) to the hepatic portal vein causes an increase in food intake. Information from the liver is conveyed to the brain via, for example, vagal pathways (vagotomy nulls these actions). Thus, a neuronal link exists between periphery and the brain. Perhaps the most complex mechanisms rely on hormones released from the periphery that act on the brain or peripheral organs.
Overall, a need exists for improved therapies to address disorders associated with food intake and metabolism. In particular, such improved therapies should aim to increase responder rate. In other words, a high probability of success should exist for a therapeutic system prior to implantation of the system. Various exemplary devices, methods, systems, etc., described below aim to provide for multiple therapies to address such issues.